Improper expression of insulin receptors on fibroblasts from a leprechaun patient

Leprechaunism is an inherited human disorder characterized by severe insulin resistance. We have examined the properties of the insulin receptor in fibroblasts from a leprechaun patient. In vitro, severe insulin resistance is reflected by a low level of insulin binding to the patients fibroblasts and impaired insulin-mediated uptake of 2-deoxyglucose. Quantification of the receptor in detergent-solubilized total glycoprotein indicates a normal receptor number, in agreement with the observed normal level of insulin receptor mRNA on northern blots. The insulin-stimulated autophosphorylation of the patient's receptor shows a normal profile. The insulin receptor is present on the plasma membrane as indicated by cell-surface iodination experiments. No abnormalities in the molecular masses of the receptor's alpha and beta chains were observed. The results indicate that an apparently normal receptor is synthesized in sufficient amounts but functional expression of the receptor on the plasma membrane is impaired.